tbuckley/cabot-search huggingface dataset:
Lymphatic vessels: roles and potential therapeutic intervention in rheumatoid arthritis and osteoarthritis
Authors: Siru Zhou, Guangyu Zhao, Ran Chen, Yang Li, Junlan Huang, Liang Kuang, Dali Zhang, Zhijun Li, Haofeng Xu, Wei Xiang, Yangli Xie, Lin Chen, Zhenhong Ni
Journal: Theranostics (2023)

Lymphatic vessel networks are a main part of the vertebrate cardiovascular system, which participate in various physiological and pathological processes via regulation of fluid transport and immunosurveillance.Targeting lymphatic vessels has become a potent strategy for treating various human diseases.The presence of varying degrees of inflammation in joints of rheumatoid arthritis (RA) and osteoarthritis (OA), characterized by heightened infiltration of inflammatory cells, increased levels of inflammatory factors, and activation of inflammatory signaling pathways, significantly contributes to the disruption of cartilage and bone homeostasis in arthritic conditions.Increasing evidence has demonstrated the pivotal role of lymphatic vessels in maintaining joint homeostasis, with their pathological alterations closely associated with the initiation and progression of inflammatory joint diseases.In this review, we provide a comprehensive overview of the evolving knowledge regarding the structural and functional aspects of lymphatic vessels in the pathogenesis of RA and OA.In addition, we summarized the potential regulatory mechanisms underlying the modulation of lymphatic function in maintaining joint homeostasis during inflammatory conditions, and further discuss the distinctions between RA and OA.Moreover, we describe therapeutic strategies for inflammatory arthritis based on lymphatic vessels, including the promotion of lymphangiogenesis, restoration of proper lymphatic vessel function through anti-inflammatory approaches, enhancement of lymphatic contractility and drainage, and alleviation of congestion within the lymphatic system through the elimination of inflammatory cells.At last, we envisage potential research perspectives and strategies to target lymphatic vessels in treating these inflammatory joint diseases.
Red blood cells in biology and translational medicine: natural vehicle inspires new biomedical applications
Authors: Xueyun Zhang, Yindan Lin, Jinxia Xin, Ying Zhang, Kaiwen Yang, Yan Luo, Ben Wang
Journal: Theranostics (2023)

Red blood cells (RBCs) are the most abundant cell type in the blood, and play a critical role in oxygen transport.With the development of nanobiotechnology and synthetic biology, scientists have found multiple ways to take advantage of the characteristics of RBCs, such as their long circulation time, to construct universal RBCs, develop drug delivery systems, and transform cell therapies for cancer and other diseases.This article reviews the component and aging mystery of RBCs, the methods for the applied universal RBCs, and the application prospects of RBCs, such as the engineering modification of RBCs used in cytopharmaceuticals for drug delivery and immunotherapy.Finally, we summarize some perspectives on the biological features of RBCs and provide further insights into translational medicine.
LCP1 knockdown in monocyte-derived macrophages: mitigating ischemic brain injury and shaping immune cell signaling and metabolism
Authors: Yan Wang, Qianqian Yin, Decao Yang, Haojie Jin, Yang Yao, Jibing Song, Cuiying Liu, Yu Nie, Hao Yin, Wei Wang, Baohui Xu, Lixiang Xue, Xunming Ji, Xiaoyuan Chen, Heng Zhao
Journal: Theranostics (2023)

Ischemic stroke poses a significant health burden with limited treatment options. Lymphocyte Cytosolic Protein 1 (LCP1) facilitates cell migration and immune responses by aiding in actin polymerization, cytoskeletal rearrangements, and phagocytosis. We have demonstrated that the long non-coding RNA (lncRNA) Maclpil silencing in monocyte-derived macrophages (MoDMs) led to LCP1 inhibition, reducing ischemic brain damage. However, the role of LCP1 of MoDMs in ischemic stroke remains unknown.
Reprogramming of endothelial gene expression by tamoxifen inhibits angiogenesis and ERα-negative tumor growth
Authors: Chanaëlle Fébrissy, Marine Adlanmerini, Christel Péqueux, Frédéric Boudou, Mélissa Buscato, Adrien Gargaros, Silveric Gilardi-Bresson, Khrystyna Boriak, Henrik Laurell, Coralie Fontaine, Benita S. Katzenellenbogen, John A. Katzenellenbogen, Julie Guillermet-Guibert, Jean-François Arnal, Raphaël Metivier, Françoise Lenfant
Journal: Theranostics (2023)

: 17β-estradiol (E2) can directly promote the growth of ERα-negative cancer cells through activation of endothelial ERα in the tumor microenvironment, thereby increasing a normalized tumor angiogenesis. ERα acts as a transcription factor through its nuclear transcriptional AF-1 and AF-2 transactivation functions, but membrane ERα plays also an important role in endothelium. The present study aims to decipher the respective roles of these two pathways in ERα-negative tumor growth. Moreover, we delineate the actions of tamoxifen, a Selective Estrogen Receptor Modulator (SERM) in ERα-negative tumors growth and angiogenesis, since we recently demonstrated that tamoxifen impacts vasculature functions through complex modulation of ERα activity.
Altered plasma protein profiles in genetic FTD – a GENFI study
Authors: Abbe Ullgren, Linn Öijerstedt, Jennie Olofsson, Sofia Bergström, Julia Remnestål, John C van Swieten, Lize C Jiskoot, Harro Seelaar, Barbara Borroni, Raquel Sanchez-Valle, Fermin Moreno, Robert Laforce, Matthis Synofzik, Daniela Galimberti, James B Rowe, Mario Masellis, Maria Carmela Tartaglia, Elizabeth Finger, Rik Vandenberghe, Alexandre de Mendonça, Pietro Tirabosch, Isabel Santana, Simon Ducharme, Chris R Butler, Alexander Gerhard, Markus Otto, Arabella Bouzigues, Lucy Russell, Imogen J Swift, Aitana Sogorb-Esteve, Carolin Heller, Jonathan D Rohrer, Anna Månberg, Peter Nilsson, Caroline Graff
Journal: Molecular Neurodegeneration (2023)

Abstract Background Plasma biomarkers reflecting the pathology of frontotemporal dementia would add significant value to clinical practice, to the design and implementation of treatment trials as well as our understanding of disease mechanisms. The aim of this study was to explore the levels of multiple plasma proteins in individuals from families with genetic frontotemporal dementia. Methods Blood samples from 693 participants in the GENetic Frontotemporal Dementia Initiative study were analysed using a multiplexed antibody array targeting 158 proteins. Results We found 13 elevated proteins in symptomatic mutation carriers, when comparing plasma levels from people diagnosed with genetic FTD to healthy non-mutation controls and 10 proteins that were elevated compared to presymptomatic mutation carriers. Conclusion We identified plasma proteins with altered levels in symptomatic mutation carriers compared to non-carrier controls as well as to presymptomatic mutation carriers. Further investigations are needed to elucidate their potential as fluid biomarkers of the disease process.
Phase II study of high-dose hyperfractionated radiation therapy for grade 3 glioma
Authors: T. Nomiya, T. Kumabe, K. Nemoto, Y. Takai, S. Yamada
Journal: Journal of Clinical Oncology (2005)

1559 Background: The purpose of this study was to evaluate the efficacy of high-dose hyperfractionated radiation therapy (HFRT) for primary intra-cranial malignant glioma. Methods: From July 1995, 51 consecutive patients with histologically proven grade 3 glioma were eligible for this study (HFRT group). Patients were postoperatively irradiated with extended local field during treatment. Standard regimen of radiation therapy in this protocol was 72 Gy in 60 fractions (120 cGy /fraction, 2 fractions /day). Patients with grade 3 glioma in brain stem were excluded because of its intolerability of full-dose irradiation. Data of 90 patients whom treated previously in our institution was used as a control group. The primary endpoint was local control rate (LCR) and the secondary endpoints were overall survival (OS), progression-free survival (PFS), and late toxicity. Results: Mean biologically equivalent doses of external beam of HFRT group and control group were 68.5 Gy and 61.2 Gy, respectively (p=0.0003: unpaired-t test). No significant differences in age, gender, performance status, and extent of surgery were found between HFRT group and control group. 5-year OS of HFRT group and control group were 56% and 31%, respectively (p=0.024: logrank test). 5-year PFS of HFRT group and control group were 51% and 27%, respectively (p=0.049: logrank test). 5-year LCR of HFRT group and control group were 79% and 33%, respectively (p=0.0005: logrank test). Total failure at 5-year of HFRT group and control group were 17 (33%) and 55 (66%), respectively (p=0.0002: chi-square test). Inside-irradiation field failure and outside-irradiation field failure were 9 (18%) and 11 (22%) in HFRT group, and 53 (59%) and 6 (7%) in control group, respectively. Late toxicity (radiation-induced brain necrosis) were observed in 2 (4%) in HFRT group and 5 (6%) in control group (N.S.). Conclusions: The results of this study showed that high-dose hyperfractionated radiation therapy significantly improved OS, PFS and LCR of grade 3 glioma with tolerable toxicity. We conclude that high-dose hyperfractionated radiation therapy can be a new standard regimen for the treatment of grade 3 glioma. No significant financial relationships to disclose.
Frequency of bloodstream infections caused by six key antibiotic-resistant pathogens for prioritization of research and discovery of new therapies in Europe: a systematic review
Authors: Maria Diletta Pezzani, Fabiana Arieti, Nithya Babu Rajendran, Benedetta Barana, Eva Cappelli, Maria Elena De Rui, Liliana Galia, Nasreen Hassoun-Kheir, Lorenzo Argante, Johannes Schmidt, Jesus Rodriguez-Bano, Stephan Harbarth, Marlieke de Kraker, Beryl Primrose Gladstone, Evelina Tacconelli
Journal: Clinical Microbiology and Infection (2023)

To prioritize healthcare investments, ranking of infections caused by antibiotic-resistant bacteria should be based on accurate incidence data.
Raising NAD <sup>+</sup> Level Stimulates Short-Chain Dehydrogenase/Reductase Proteins to Alleviate Heart Failure Independent of Mitochondrial Protein Deacetylation
Authors: Matthew A. Walker, Hongye Chen, Aprajita Yadav, Julia Ritterhoff, Outi Villet, Tim McMillen, Yuliang Wang, Hayley Purcell, Danijel Djukovic, Daniel Raftery, Nina Isoherranen, Rong Tian
Journal: Circulation (2023)

Strategies to increase cellular NAD
Avoiding Extinction: Cancer-Associated Fibroblasts Help Triple-Negative Breast Cancer Outrun Chemotherapy
Authors: Steven W. Wall, Gloria V. Echeverria
Journal: Cancer Research (2023)

Abstract Neoadjuvant chemotherapy is a staple of triple-negative breast cancer (TNBC) treatment. Predicated on the principle of fractional cell killing, chemotherapy regimens are typically cycles of short drug exposure followed by a period of recovery from the toxic side effects. However, many patients experience chemotherapy resistance for a variety of reasons, resulting in tumors that are not sufficiently reduced with treatment. Response to chemotherapy prior to surgical resection is a strong predictor of patient prognosis; therefore, finding ways to improve efficacy is a critical need. Tremendous effort has gone into understanding the relationship between the tumor microenvironment and treatment sensitivity in many tumor types. In this issue of Cancer Research, Miroshnychenko and colleagues investigate how the well-characterized phenomenon of cancer-associated fibroblast (CAF)–induced proliferation of tumor cells allows TNBC to evade extinction after multiple cycles of cytotoxic chemotherapies. Their findings imply CAF-promoted tumor cell proliferation allows tumor cells to push through stressful conditions caused by treatment and to avoid tumor elimination. This mechanism of ‘indirect’ chemoresistance contrasts with the dogma that tumor cell proliferation enhances chemosensitivity. This study opens the door for the discovery of mechanisms and therapeutic targets to limit the ability of CAFs to rescue tumor cells from the brink of extinction. See related article by Miroshnychenko et al., p. 3681
Modeling personalized heart rate response to exercise and environmental factors with wearables data
Authors: Achille Nazaret, Sana Tonekaboni, Gregory Darnell, Shirley You Ren, Guillermo Sapiro, Andrew C. Miller
Journal: npj Digital Medicine (2023)

Heart rate (HR) response to workout intensity reflects fitness and cardiorespiratory health. Physiological models have been developed to describe such heart rate dynamics and characterize cardiorespiratory fitness. However, these models have been limited to small studies in controlled lab environments and are challenging to apply to noisy-but ubiquitous-data from wearables. We propose a hybrid approach that combines a physiological model with flexible neural network components to learn a personalized, multidimensional representation of fitness. The physiological model describes the evolution of heart rate during exercise using ordinary differential equations (ODEs). ODE parameters are dynamically derived via a neural network connecting personalized representations to external environmental factors, from area topography to weather and instantaneous workout intensity. Our approach efficiently fits the hybrid model to a large set of 270,707 workouts collected from wearables of 7465 users from the Apple Heart and Movement Study. The resulting model produces fitness representations that accurately predict full HR response to exercise intensity in future workouts, with a per-workout median error of 6.1 BPM [4.4-8.8 IQR]. We further demonstrate that the learned representations correlate with traditional metrics of cardiorespiratory fitness, such as VO2 max (explained variance 0.81 ± 0.003). Lastly, we illustrate how our model is naturally interpretable and explicitly describes the effects of environmental factors such as temperature and humidity on heart rate, e.g., high temperatures can increase heart rate by 10%. Combining physiological ODEs with flexible neural networks can yield interpretable, robust, and expressive models for health applications.
Microbial Regulation of Vitamin D Linked to Colorectal Cancer: A Sex Bias
Authors: Erick Riquelme, Rian M. Howell, Florencia McAllister
Journal: Cancer Research (2023)

Abstract In a recent issue of Cancer Cell, Li and colleagues revealed that Carnobacterium maltaromaticum (C. maltaromaticum) was significantly depleted in the stool samples of patients with colorectal cancer in a female-specific manner. C. maltaromaticum actively participated in the generation of vitamin D intermediary metabolites, which together with Faecalibacterium prausnitzii and Lachnispiraceae bacterium produce an active metabolite of vitamin D that protects against colorectal cancer development. C. maltaromaticum supplementation induced in a female-specific manner an increase in vitamin D levels that would activate its receptor in the colonic epithelium, protecting against the development of colorectal cancer.
The role of admixture in the rare variant contribution to inflammatory bowel disease
Authors: Courtney Astore, Shivam Sharma, Sini Nagpal, David J. Cutler, John D. Rioux, Judy H. Cho, Dermot P. B. McGovern, Steven R. Brant, Subra Kugathasan, I. King Jordan, Greg Gibson
Journal: Genome Medicine (2023)

Abstract Background Identification of rare variants involved in complex, polygenic diseases like Crohn’s disease (CD) has accelerated with the introduction of whole exome/genome sequencing association studies. Rare variants can be used in both diagnostic and therapeutic assessments; however, since they are likely to be restricted to specific ancestry groups, their contributions to risk assessment need to be evaluated outside the discovery population. Prior studies implied that the three known rare variants in NOD2 are absent in West African and Asian populations and only contribute in African Americans via admixture. Methods Whole genome sequencing (WGS) data from 3418 African American individuals, 1774 inflammatory bowel disease (IBD) cases, and 1644 controls were used to assess odds ratios and allele frequencies (AF), as well as haplotype-specific ancestral origins of European-derived CD variants discovered in a large exome-wide association study. Local and global ancestry was performed to assess the contribution of admixture to IBD contrasting European and African American cohorts. Results Twenty-five rare variants associated with CD in European discovery cohorts are typically five-fold lower frequency in African Americans. Correspondingly, where comparisons could be made, the rare variants were found to have a predicted four-fold reduced burden for IBD in African Americans, when compared to European individuals. Almost all of the rare CD European variants were found on European haplotypes in the African American cohort, implying that they contribute to disease risk in African Americans primarily due to recent admixture. In addition, proportion of European ancestry correlates the number of rare CD European variants each African American individual carry, as well as their polygenic risk of disease. Similar findings were observed for 23 mutations affecting 10 other common complex diseases for which the rare variants were discovered in European cohorts. Conclusions European-derived Crohn’s disease rare variants are even more rare in African Americans and contribute to disease risk mainly due to admixture, which needs to be accounted for when performing cross-ancestry genetic assessments.
In Vivo Base Editing of <i>Scn5a</i> Rescues Type 3 Long QT Syndrome in Mice
Authors: Man Qi, Shuhong Ma, Jingtong Liu, Xujie Liu, Jingjing Wei, Wen-Jing Lu, Siyao Zhang, Yun Chang, Yongshuai Zhang, Kejia Zhong, Yuting Yan, Min Zhu, Yabing Song, Yundai Chen, Guoliang Hao, Jianbin Wang, Li Wang, Andrew S. Lee, Xiangbo Chen, Yongming Wang, Feng Lan
Journal: Circulation (2023)

Pathogenic variants in
Spatial transcriptomics reveals a low extent of transcriptionally active hepatitis B virus integration in patients with HBsAg loss
Authors: Xiaoqi Yu, Qiming Gong, Demin Yu, Yongyan Chen, Ying Jing, Fabien Zoulim, Xinxin Zhang
Journal: Gut (2023)

Objective Hepatitis B virus (HBV) can integrate into the chromosomes of infected hepatocytes, contributing to the production of hepatitis B surface antigen (HBsAg) and to hepatocarcinogenesis. In this study, we aimed to explore whether transcriptionally active HBV integration events spread throughout the liver tissue in different phases of chronic HBV infection, especially in patients with HBsAg loss. Design We constructed high-resolution spatial transcriptomes of liver biopsies containing 13 059 tissue spots from 18 patients with chronic HBV infection to analyse the occurrence and relative distribution of transcriptionally active viral integration events. Immunohistochemistry was performed to evaluate the expression of HBsAg and HBV core antigen. Intrahepatic covalently closed circular DNA (cccDNA) levels were quantified by real-time qPCR. Results Spatial transcriptome sequencing identified the presence of 13 154 virus-host chimeric reads in 7.86% (1026 of 13 059) of liver tissue spots in all patients, including three patients with HBsAg loss. These HBV integration sites were randomly distributed on chromosomes and can localise in host genes involved in hepatocarcinogenesis, such as ALB, CLU and APOB . Patients who were receiving or had received antiviral treatment had a significantly lower percentage of viral integration-containing spots and significantly fewer chimeric reads than treatment-naïve patients. Intrahepatic cccDNA levels correlated well with viral integration events. Conclusion Transcriptionally active HBV integration occurred in chronically HBV-infected patients at different phases, including in patients with HBsAg loss. Antiviral treatment was associated with a decreased number and extent of transcriptionally active viral integrations, implying that early treatment intervention may further reduce the number of viral integration events.
#ReadyToPlay: health problems in women’s football–a two-season prospective cohort study in the Norwegian premier league
Authors: Roar Amundsen, Solveig Thorarinsdottir, Benjamin Clarsen, Thor Einar Andersen, Merete Møller, Roald Bahr
Journal: British Journal of Sports Medicine (2023)

To describe the prevalence, incidence and burden of all health problems in the Norwegian women's premier league.During the 2020 and 2021 seasons, players in the Norwegian women's premier league reported all health problems (sudden-onset injuries, gradual-onset injuries and illnesses) weekly, using the Oslo Sports Trauma Research Centre Questionnaire on Health Problems. Team medical staff diagnosed reported problems using the Sport Medicine Diagnostic Coding System. We calculated average weekly prevalence, incidence and burden of all health problems reported.We included 294 players (age: 22±4 years) from 11 teams. Response rate to the weekly questionnaire was 79%. On average, 32% (95% CI: 31% to 33%) of the players reported at least one health problem at any time and 22% (95% CI: 21% to 23%) reported a substantial health problem negatively affecting their training volume or performance. The overall incidence was 10.7 health problems per 1000 hours of football exposure. Sudden-onset injuries were most severe (68% of the total time loss), followed by gradual-onset injuries (25%) and illnesses (8%). Thigh was the most common injury location (26%), while knee injuries were most severe, causing 42% of the total injury time loss. Anterior cruciate ligament (ACL) injuries alone caused 30% of the total injury time loss.One in five players had a health problem negatively affecting their training volume or performance at any time. Sudden-onset injuries represented the most burdensome health problem. Thigh injuries were most frequent, while knee injuries, ACL injuries especially, were most severe.
Ginsenoside modified lipid-coated perfluorocarbon nanodroplets: A novel approach to reduce complement protein adsorption and prolong in vivo circulation
Authors: Jie Zhou, Binyang Gao, Huan Zhang, Rui Yang, Jianbo Huang, Xin Li, Yi Zhong, Yan Wang, Xiaoxia Zhu, Yan Luo, Feng Yan
Journal: Acta Pharmaceutica Sinica B (2023)

Lipid-coated perfluorocarbon nanodroplets (lp-NDs) hold great promise in bio-medicine as vehicles for drug delivery, molecular imaging and vaccine agents. However, their clinical utility is restricted by limited targeted accumulation, attributed to the innate immune system (IIS), which acts as the initial defense mechanism in humans. This study aimed to optimize lp-ND formulations to minimize non-specific clearance by the IIS. Ginsenosides (Gs), the principal components of
Epigenetic mechanisms underlying sex differences in the brain and behavior
Authors: Marija Kundakovic, Maria Tickerhoof
Journal: Trends in Neurosciences (2023)

Sex differences are found across brain regions, behaviors, and brain diseases. Sexual differentiation of the brain is initiated prenatally but it continues throughout life, as a result of the interaction of three major factors: gonadal hormones, sex chromosomes, and the environment. These factors are thought to act, in part, via epigenetic mechanisms which control chromatin and transcriptional states in brain cells. In this review, we discuss evidence that epigenetic mechanisms underlie sex-specific neurobehavioral changes during critical organizational periods, across the estrous cycle, and in response to diverse environments throughout life. We further identify future directions for the field that will provide novel mechanistic insights into brain sex differences, inform brain disease treatments and women's brain health in particular, and apply to people across genders.